The object of this proposal is to investigate further the prevention of murine lupus nephritis in (NZB x NZW)F1 mice by inducing carrier determined immunologic tolerance to denatured DNA (D-DNA). This can be accomplished by the administration of the nucleosides adenosine, guanosine, cytosine and thymine riboside covalently bound to isogeneic IgG (NZB xNZW)F1 mice which receive the tetranucleoside isogeneic IgG from birth to 5 months of age fail to make antibody to D-DNA. In contrast, BWF1 mice similarly treated with tetranucleoside bovine serum albumin or tetranucleoside without carrier, produce anti DNA antibody equivalent to that of untreated BWF 1 control mice. Furthermore, only mice rendered tolerant of D-DNA by tetranucleoside isogeneic IgG failed to develop the chronic membranous glomerulonephritis which characterizes the renal lesions in these animals. Thus, the eventual goal is to reverse the disease (murine SLE) to which BWF1 hybrid mice have been genetically predisposed by utilizing the concept of carrier determined tolerance to nucleic acids as an initial step toward development of new therapeutic regimens for human SLE. In addition, the relationships of antibodies to nuclei acids to the role of latent murine viral infections in the pathogenesis of the lesion of murine SLE will be studied.